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Biomedicines 2021 Sep 06;99:. doi: 10.3390/biomedicines9091172.
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Characterization of a Compound Heterozygous SLC2A9 Mutation That Causes Hypouricemia.

Yoon J , Cachau R , David VA , Thompson M , Jung W , Jee SH , Daar IO , Winkler CA , Cho SK .

Renal hypouricemia is a rare genetic disorder. Hypouricemia can present as renal stones or exercise-induced acute renal failure, but most cases are asymptomatic. Our previous study showed that two recessive variants of SLC22A12 (p.Trp258*, pArg90His) were identified in 90% of the hypouricemia patients from two independent cohorts: the Korean genome and epidemiology study (KoGES) and the Korean Cancer Prevention Study (KCPS-II). In this work, we investigate the genetic causes of hypouricemia in the rest of the 10% of unsolved cases. We found a novel non-synonymous mutation of SLC2A9 (voltage-sensitive uric acid transporter) in the whole-exome sequencing (WES) results. Molecular dynamics prediction suggests that the novel mutation p.Met126Val in SLCA9b (p.Met155Val in SLC2A9a) hinders uric acid transport through a defect of the outward open geometry. Molecular analysis using Xenopus oocytes confirmed that the p.Met126Val mutation significantly reduced uric acid transport but does not affect the SLC2A9 protein expression level. Our results will shed light on a better understanding of SLC2A9-mediated uric acid transport and the development of a uric acid-lowering agent.

PubMed ID: 34572357
PMC ID: PMC8471325
Article link: Biomedicines

Genes referenced: asb12 asic3 dnai1 gpr101 pik3cb ppef1 pwwp2b rbm12 rlim slc2a9

Disease Ontology terms: urolithiasis [+]

Article Images: [+] show captions
References [+] :
Adzhubei, A method and server for predicting damaging missense mutations. 2010, Pubmed